Avaliação do potencial de derivados do ácido kójico sobre a melanogênese e o envelhecimento cutâneo

Abstract

The continuous sun exposure is a major factor causing oxidative stress, stains and aging skin. The growth of the cosmetics market in the world, the growing interest of people for youthful skin, free of wrinkles and spots, has stimulated researchers to search for new assets for this purpose. Kojic acid is a well known and widely used depigmenting, mainly produced by fungi of the genus Aspergillus which has also been reported as an antioxidant and rejuvenating. However, kojic acid has disadvantages such as low stability and poor inhibition at low concentrations which encourages researchers to search for more active compounds or changes in the molecule in order to seek more active derivatives, stable and secure. Thus, this work aimed at studying the potential of nine Kojic acid derivatives synthesized by researchers at the Federal University of Pará - UFPA in order to obtain compounds with depigmenting activity, antioxidants and rejuvenating superior to those reported kojic acid. In this study we performed cytotoxicity assays, evaluation of antioxidant activity in vitro and enzyme in vitro inhibition of elastase, tyrosinase, collagenase and hyaluronidase. We evaluated the inhibition of tyrosinase activity and melanin production in B16F10 and alterations on tyrosinase gene expression. Of the nine derivatives studied, only three of them, kojato zinc, kojato copper (Cu-AK) and oleikojato copper (Cu-Ok), showed in vitro inhibitory activity on mushroom tyrosinase and were selected for the present study. The inhibition of tyrosinase in vitro kojato zinc (IC 50 - 30.4 ± 0.89µM) was higher than that presented by the kojic acid (IC50 - 60.2 ± 1.83µM) and its other derivatives Cu-AK (IC50 – 133.3 ± 6.59µM) and Cu-Ok (IC50 - 77.6 ± 4.31µM). These compounds were not cytotoxic to B16F10 cells and human dermal fibroblasts at 100 µM and showed no hemolytic potential at the concentration of 250 µM. The Kojic acid and derivatives, Cu-AK and Cu-Ok, were selected to evaluate the action on melanogenesis and enzymes that act on skin aging, as well as antioxidant activity. AK, AK-Cu and Cu-OK, apresenaram low antioxidant activity in the DPPH assay at 50 µg/mL, however, proved to be powerful metal chelating agents. In the studied concentration, 50 µg/mL, OK-Cu (76.0 ± 5.7%) showed chelating activity slightly higher than the AK (58.9 ± 5.63%) and AK-Cu (57.4 ± 5 24). The tyrosinase activity in B16F10 was strongly inhibited by Cu-AK (86.7%) and Cu- OK (92.5%), melanin production decreased by approximately 60.2% and 61.6% respectively. There were no changes in levels of gene expression of tyrosinase and there was no significant inhibition of other enzymes studied. Our results suggest that the action on melanogenesis observed for Cu-OK and Cu-AK occurs through inhibition of tyrosinase associated with an antioxidant mechanism. The compounds studied have great potential for use as cosmetic depigmenting agents.